TY - JOUR
T1 - JAK inhibitor therapy in a child with inherited usp18 deficiency
AU - Alsohime, Fahad
AU - Martin-Fernandez, Marta
AU - Temsah, Mohamad Hani
AU - Alabdulhafid, Majed
AU - Le Voyer, Tom
AU - Alghamdi, Malak
AU - Qiu, Xueer
AU - Alotaibi, Najla
AU - Alkahtani, Areej
AU - Buta, Sofija
AU - Jouanguy, Emmanuelle
AU - Al-Eyadhy, Ayman
AU - Gruber, Conor
AU - Hasan, Gamal M.
AU - Bashiri, Fahad A.
AU - Halwani, Rabih
AU - Hassan, Hamdy H.
AU - Al-Muhsen, Saleh
AU - Alkhamis, Nouf
AU - Alsum, Zobaida
AU - Casanova, Jean Laurent
AU - Bustamante, Jacinta
AU - Bogunovic, Dusan
AU - Alangari, Abdullah A.
N1 - Funding Information:
Supported by a grant (RGP-190, to Dr. Alangari) from the Deanship of Scientific Research, King Saud University, Riyadh, Saudi Arabia; by grants (R01AI127372, R21AI134366, and R21AI129827, to Dr. Bogunovic) from the National Institute of Allergy and Infectious Diseases, National Institutes of Health; and by the Hirschl Scholar Award and the March of Dimes (to Dr. Bogunovic). The Laboratory of Human Genetics of Infectious Diseases is supported by grants from the St. Giles Foundation, the Jeffrey Modell Foundation, and the Rockefeller University Center for Clinical and Translational Science; by a grant (8UL1TR000043) from the National Center for Research Resources and the National Center for Advancing Sciences; by grants (5R01AI089970-02 and 5R37AI095983) from the National Institute of Allergy and Infectious Diseases; and by the French National Research Agency through a grant (ANR-10-LABX-62-IBEID) from the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence, a grant (ANR-10-IAHU-01) from the “Investments for the Future” program, and a grant (ANR-16-CE17-0005-01, to Dr. Bustamante) from GENMSMD (Human Genetic Dissection of Mendelian Susceptibility to Mycobacterial Disease).
Publisher Copyright:
© 2020 Massachusetts Medical Society.
PY - 2020/1/16
Y1 - 2020/1/16
N2 - Deficiency of ubiquitin-specific peptidase 18 (USP18) is a severe type I interferonopathy. USP18 down-regulates type I interferon signaling by blocking the access of Janus-associated kinase 1 (JAK1) to the type I interferon receptor. The absence of USP18 results in unmitigated interferon-mediated inflammation and is lethal during the perinatal period. We describe a neonate who presented with hydrocephalus, necrotizing cellulitis, systemic inflammation, and respiratory failure. Exome sequencing identified a homozygous mutation at an essential splice site on USP18. The encoded protein was expressed but devoid of negative regulatory ability. Treatment with ruxolitinib was followed by a prompt and sustained recovery.
AB - Deficiency of ubiquitin-specific peptidase 18 (USP18) is a severe type I interferonopathy. USP18 down-regulates type I interferon signaling by blocking the access of Janus-associated kinase 1 (JAK1) to the type I interferon receptor. The absence of USP18 results in unmitigated interferon-mediated inflammation and is lethal during the perinatal period. We describe a neonate who presented with hydrocephalus, necrotizing cellulitis, systemic inflammation, and respiratory failure. Exome sequencing identified a homozygous mutation at an essential splice site on USP18. The encoded protein was expressed but devoid of negative regulatory ability. Treatment with ruxolitinib was followed by a prompt and sustained recovery.
UR - http://www.scopus.com/inward/record.url?scp=85077940751&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1905633
DO - 10.1056/NEJMoa1905633
M3 - Article
C2 - 31940699
AN - SCOPUS:85077940751
SN - 0028-4793
VL - 382
SP - 256
EP - 265
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 3
ER -